Citations

ObjectiveIt is unclear why despite a comparable cardiometabolic risk profile, “metabolically benign” overweight/obese individuals show an elevated risk of cardiovascular disease compared to normal weight individuals.Design and MethodsIn cross‐sectional analyses, we compared levels of ectopic fat (epicardial, pericardial, and hepatic fat) and adipokines (leptin, soluble leptin receptor, and high molecular weight [HMW] adiponectin) among metabolically benign (MBO) and at‐risk overweight/obese (ARO), and metabolically benign normal weight (MBNW) women, screened for the Kronos Early Estrogen Prevention Study. We defined “metabolically benign” with ≤ 1, and “at‐risk” with ≥2 components of the metabolic syndrome.ResultsCompared to MBO women, ARO women had significantly elevated odds of being in the top tertile of epicardial fat (OR: 1.76, 95% CI: 1.04‐2.99), hepatic fat (OR: 1.90, 95% CI:1.12‐3.24) and leptin (OR: 2.15, 95% CI: 1.23‐3.76), and the bottom tertile of HMW‐adiponectin (OR: 2.90, 95% CI: 1.62‐5.19). Compared to MBNW women, MBO women had significantly higher odds of being in the top tertile of epicardial fat (OR: 5.17, 95% CI: 3.22‐8.29), pericardial fat (OR: 9.27, 95% CI: 5.52‐15.56) and hepatic fat (OR: 2.72, 95% CI: 1.77‐4.19) and the bottom tertile of HMW adiponectin levels (OR: 2.51, 95% CI: 1.60‐3.94).ConclusionsLevels of ectopic fat and the adverse adipokine profile increase on a continuum of BMI, suggesting that the metabolically benign phenotype may be a transient state.

Abstract Background: Colorectal cancer (CRC) in densely affected families without Lynch Syndrome may be due to mutations in undiscovered genetic loci. Familial linkage analyses have yielded disparate results; the use of exome sequencing in coding regions may identify novel segregating variants. Methods: We completed exome sequencing on 40 affected cases from 16 multicase pedigrees to identify novel loci. Variants shared among all sequenced cases within each family were identified and filtered to exclude common variants and single-nucleotide variants (SNV) predicted to be benign. Results: We identified 32 nonsense or splice-site SNVs, 375 missense SNVs, 1,394 synonymous or noncoding SNVs, and 50 indels in the 16 families. Of particular interest are two validated and replicated missense variants in CENPE and KIF23, which are both located within previously reported CRC linkage regions, on chromosomes 1 and 15, respectively. Conclusions: Whole-exome sequencing identified DNA variants in multiple genes. Additional sequencing of these genes in additional samples will further elucidate the role of variants in these regions in CRC susceptibility. Impact: Exome sequencing of familial CRC cases can identify novel rare variants that may influence disease risk. Cancer Epidemiol Biomarkers Prev; 22(7); 1239–51. ©2013 AACR.

BACKGROUND Maintaining consistency of results over time is a challenge in laboratory medicine. Lot-to-lot reagent changes are a major threat to consistency of results. METHODS For the period October 2007 through July 2012, we reviewed lot validation data for each new lot of insulin-like growth factor 1 (IGF-1) reagents (Siemens Healthcare Diagnostics) at Mayo Clinic, Rochester, MN, and the University of Virginia, Charlottesville, VA. Analyses of discarded patient samples were used for comparison of lots. For the same period, we determined the distributions of reported patient results for each lot of reagents at the 2 institutions. RESULTS Lot-to-lot validation studies identified no reagent lot as significantly different from the preceding lot. By contrast, significant lot-to-lot changes were seen in the means and medians of 105 668 reported patient IGF-I results during the period. The frequency of increased results increased nearly 2-fold to a high of 17%, without detectable changes in the underlying patient demographics. Retrospective statistical analysis indicated that lot-to-lot comparison protocols were underpowered and that validation studies for this assay required testing >100 samples to achieve 90% power to detect reagent lots that would significantly alter the distributions of patient results. CONCLUSIONS The number of test samples required for adequate lot-to-lot validation protocols is high and may be prohibitively large, especially for low-volume or complex assays. Monitoring of the distributions of patient results has the potential to detect lot-to-lot inconsistencies relatively quickly. We recommend that manufacturers implement remote monitoring of patient results from analyzers in multiple institutions to allow rapid identification of between-lot result inconsistency.

BackgroundThe AMICUS (Fenwal, Inc.) was cleared in the United States for platelet (PLT) and plasma collection in 1996 with subsequent clearances for the collection of other blood products. Although not previously used for therapeutic plasma exchange (TPE), new disposables, software, and hardware were developed to enable TPE on the AMICUS.Study Design and MethodsA multicenter, randomized, nonblinded, crossover paired treatment protocol was performed. Thirty patients with orders for at least two TPE procedures were randomly assigned to the AMICUS or the COBE Spectra (TerumoBCT) for the first treatment. Each patient was crossed over to the other device using the same procedure settings from the first procedure. The primary objective compared efficiency of plasma removal (EPR) with secondary objectives of comparing PLT and hemoglobin (Hb) waste plasma content, coagulation factor and complement activation, fluid balance tracking accuracy, procedure length, and adverse events.ResultsThe EPR for the AMICUS (81.9 ± 7.62%) was superior to that of the COBE Spectra (75.2 ± 6.29%; p = 0.00001). The AMICUS also demonstrated statistically higher fluid balance accuracy (99.84%) compared to that of the COBE Spectra (98.83%; p < 0.0001) and a statistically shorter procedure time (103.9 ± 30.8 vs. 110.5 ± 27.1 min, p < 0.001). No significant differences with regard to PLT and Hb content in the waste plasma, change in patient PLT count, or changes in markers of coagulation and complement cascade activation were seen. Frequency and severity of adverse reactions were similar.ConclusionThe AMICUS separator can effectively perform TPE. The AMICUS demonstrated superior plasma removal efficiency compared to the COBE Spectra with no evidence of significant differences in PLT removal, hemolysis, and coagulation or complement activation.